{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:36:05Z","timestamp":1786700165549,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"30","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82304425"],"award-info":[{"award-number":["82304425"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Although cGAS\u2010STING immunotherapy holds immense potential, its efficacy is severely compromised by pathway evasion. To overcome this, we engineered a core\u2010shell bilayer nanobomb (M\/ZIF\/MnO\n                    <jats:sub>2<\/jats:sub>\n                    @DBCO) via a template\u2010assisted approach, integrating MSC1094308 into ZIF\u20108 cores followed by MnO\n                    <jats:sub>2<\/jats:sub>\n                    shell deposition and DBCO functionalization. In a simulated tumor microenvironment, ZIF\u20108 loading accelerated Mn\n                    <jats:sup>2+<\/jats:sup>\n                    release from MnO\n                    <jats:sub>2<\/jats:sub>\n                    , increasing the cumulative release by nearly 30% within 8 h compared to pristine MnO\n                    <jats:sub>2<\/jats:sub>\n                    . Cellular assays demonstrated rapid bio\u2010orthogonal targeting of azide\u2010modified tumors, achieving lysosomal escape within 6 h postuptake. Subsequently, MnO\n                    <jats:sub>2<\/jats:sub>\n                    \u2010mediated glutathione (GSH) depletion and hydroxyl radical (\u00b7OH) generation, combined with Zn\n                    <jats:sup>2+<\/jats:sup>\n                    induced mitochondrial oxidative stress, produced cytotoxic reactive oxygen species (ROS) that triggered immunogenic cell death. Furthermore, Mn\n                    <jats:sup>2+<\/jats:sup>\n                    , Zn\n                    <jats:sup>2+<\/jats:sup>\n                    , and dsDNA released from damaged mitochondria cooperatively activated the cGAS\u2010STING pathway. Concurrently, MSC1094308 inhibited ESCRT\u2010mediated negative regulation, as evidenced by a \u223c0.2 decrease in the p\u2010STING\/VPS4B\u2010RFP colocalization coefficient, confirming the blockade of cGAS\u2010STING evasion. In vivo studies revealed that the nanoplatform profoundly stimulated antitumor immunity, increasing tumor\u2010infiltrating cytotoxic T lymphocytes approximately 8\u2010fold versus untreated controls after 21 days. This work establishes an integrated strategy harnessing Zn\n                    <jats:sup>2+<\/jats:sup>\n                    \/Mn\n                    <jats:sup>2+<\/jats:sup>\n                    synergy, nanobomb reactivity, and ESCRT inhibition to circumvent cGAS\u2010STING evasion, offering a promising paradigm for cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.1002\/adhm.71433","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T04:17:56Z","timestamp":1783657076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bio\u2010orthogonal Chemistry\u2010Facilitated Zn\u2013Mn Double\u2010Layered Nanobombs Abrogate cGAS\u2010STING Evasion of Tumor Cells"],"prefix":"10.1002","volume":"15","author":[{"given":"Jiajia","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning Province P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitong","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning Province P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning Province P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning Province P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning Province P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiyang","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning Province P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingzhen","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning Province P.R. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics Auburn University 221 Parker Hall Auburn Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmacy Shenyang Pharmaceutical University 103 Wenhua Road Shenyang Liaoning Province P.R. 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